DeCure for Agammaglobulinemia 7, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for agammaglobulinemia 7, autosomal recessive — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAgammaglobulinemia 7, autosomal recessive maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for agammaglobulinemia 7, autosomal recessive is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) — PIK3R1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8W9A · 2.7 Å · ligand 6-chloranyl-3-[[(1R)-1-[2-(1,3-dihydropyrrolo[3,4-c]pyridin-2-yl)-3,6-dimethyl-4-oxidanylidene-quinazolin-8-yl]ethyl]amino]pyridine-2-carboxylic acid (UEX). Experimental structure, not a prediction.
What the evidence adds up to
In a 2016 Iranian cohort of 87 patients with congenital agammaglobulinemia, molecular investigation of 51 patients identified 39 cases with BTK mutations (including one novel mutation), 5 cases with µ-heavy chain mutations (three novel), and 1 case of Igα deficiency. The same study reported that BTK-deficient and autosomal recessive agammaglobulinemia patients differ significantly in clinical and immunologic characteristics, though no comprehensive correlation between the type of BTK mutation and severity of clinical phenotype was found. A 1960 paper describes idiopathic acquired agammaglobulinemia associated with thymoma, noting that congenital agammaglobulinemia results from a recessive sex-linked gene affecting only males and manifests in early childhood, while the acquired form can follow lymphomas, radiation, nitrogen mustards, or multiple myeloma. In a small proportion of acquired cases no cause is found.
A 2020 review characterises agammaglobulinemia as a primary antibody deficiency with severe reduction of all immunoglobulin types and absence of peripheral B cells. The review states that X-linked and various autosomal recessive or dominant mutations underlie the pathogenesis, and that affected patients present respiratory infections, gastrointestinal complications, enterovirus infections, autoimmunity, and malignancies. The disease can be controlled by different therapeutic strategies, but the review does not specify which.
No drug treatment is tested or recommended in any of these abstracts. The 1960 paper mentions nitrogen mustards only as a cause of acquired agammaglobulinemia, not as a therapy. What remains missing is any controlled trial of a drug for autosomal recessive agammaglobulinemia 7 specifically, any patient stratification by the precise genetic defect beyond the broad BTK versus autosomal recessive distinction, and any funding for such work.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1960 · 104 citations
Idiopathic Acquired Agammaglobulinemia Associated with Thymoma
AbstractAGAMMAGLOBULINEMIA is an uncommon condition the underlying mechanism of which is fairly well understood in the majority of cases. Congenital agammaglobulinemia is the result of a recessive sex-linked gene, affecting males only, and becomes clinically manifest in early childhood. The acquired form affects previously healthy males and females and is usually secondary to lymphomas, injury to lymphoid tissue by x-rays or nitrogen mustards, multiple myeloma or other diseases characterized by dysproteinemia. In a small proportion of the cases no cause for the protein disturbance can be found, these being designated as cases of "idiopathic acquired agammaglobulinemia." Forty-four such cases have . . .
Agammaglobulinemia: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management
AbstractAgammaglobulinemia is a type of primary antibody deficiencies, characterized by severe reduction in serum level of all types of immunoglobulins level and absence of B cells in the peripheral blood. X-linked and various autosomal recessive/dominant mutations have been identified underlying the pathogenesis of this disorder. Affected patients present a broad range of clinical manifestations, including respiratory infections, gastrointestinal complications, Enterovirus infections, autoimmunity, and malignancies. This disease can be controlled by different therapeutic strategies. In this review, we describe different aspects of agammaglobulinemia such as epidemiology, pathogenesis, clinical phenotype, diagnosis, management, and prognosis of congenital agammaglobulinemia.
INDIGO (University of Illinois at Chicago) · 2016 · 0 citations · open access
Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects
Abstract<b>Objectives:</b> Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton’s-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia. <b>Methods:</b> Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients. <b>Results:</b> Out of 87 patients, a molecular investigation was performed on 51 patients leading to identification of 39 cases with BTK (1 novel mutation), 5 cases of µ-heavy chain (3 novel mutations) and 1 case of Igα-deficiencies. <b>Conclusion:</b> Although there is no comprehensive correlation between type of responsible <i>BTK</i> mutation and severity of clinical phenotype, our data suggest that BTK-deficient and autosomal recessive agammaglobulinemia patients differ significantly regarding clinical/immunologic characteristics.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
